Randomized clinical trials may not accurately reflect the public health benefit of tobacco dependence pharmacotherapies when used in "real-world" clinical settings due to differences in patient selection, motivation, and adherence. To have a positive public health impact, a treatment must be accessible and acceptable to a broad range of smokers and effective under normal use conditions. The proposed project will assess primary care patients' willingness to use cessation treatment and witl determine the relative effectiveness of five cessation pharmacotherapies. This research builds on a primary care clinic-based recruitment strategy that was highly successful in a previous study. In the proposed research, 1320 primary care patients presenting for a regular outpatient visit will be recruited by medical assistants to participate in a free smoking cessation program and will be randomly assigned to one of five active pharmacotherapies: patch, lozenge, buproprion, patch+lozenge, and bupropion+lozenge (n = 264/condition). Interested participants who pass medical screening will pick up their medications at clinic pharmacies and will receive proactive telephone counseling from the Wisconsin Tobacco Quit Line. Assessment wilt be limited to preserve the generalizability of the findings, but select individual differences will be assessed pre-quit to validate algorithms designed to optimize pharmacotherapy selection for smokers based on gender, level of dependence, and other factors. Smoking behavior will be assessed at six months and one year post-quit so that abstinence rates across pharmacotherapy conditions can be compared. The cost of incorporating tobacco dependence treatment into primary care will also be estimated. In sum, this study will reveal: patient utilization of tobacco dependence treatment when integrated seamlessly into a primary care setting, the relative effectiveness of five different pharmacotherapy treatments, the utility of algorithms for assigning medications to smokers, and the cost of a novel treatment recruitment and delivery strategy.